γ-Aminobutyric acid (GABA), which is an inhibitory neurotransmitter, is released from GABAergic neurons and then removed from extracellular fluids by the action of GABA transporters located in neuronal terminals and glia cells. The mechanism of this active uptake of GABA transporters is most important for determining when neurotransmission has been accomplished.
It is known that a GABA transporter has four subtypes (GAT-1, GAT-2, GAT-3 and BGT-1). GAT-1 and GAT-3 are located in brain and retina, GAT-2 in almost all organs, and BGT-1 in kidney and brain. The GAT-1 gene was cloned from mouse (Gene Bank accession No. M92378), rat (Gene Bank accession No. M33003) and human. (Gene Bank accession No. X54673); the GAT-2 gene from 30 mouse (Gene Bank accession No. L04663) and rat (Gene Bank accession No. M95762); the GAT-3 gene from mouse (Gene Bank accession No. L04662) and rat (Gene Bank accession No. M95763); and the BGT-1 gene from mouse (Gene Bank accession No. M97632) and dog (Gene Bank accession No. M80403). However, a human GAT-2 gene is yet unknown so far.
It is an object of the present invention to provide the following:
(i) a protein containing an amino acid sequence, which is the same or substantially the same as the amino acid sequence represented by SEQ ID NO:1 (preferably, a protein having a GABA transporter activity) or its partial peptide, or its amide or ester, or a salt thereof;
(ii) a DNA encoding the protein containing an amino acid sequence, which is the same or substantially the same as the amino acid sequence represented by SEQ ID NO:1 (preferably, a protein having a GABA transporter activity) or its partial peptide;
(iii) a recombinant vector containing the DNA;
(iv) a transformant bearing the recombinant vector;
(v) a process of producing the protein containing an amino acid sequence, which is the same or substantially the same as the amino acid sequence represented by SEQ ID NO:1 (preferably, a protein having a GABA transporter activity) or a salt thereof;
(vi) an antibody to the protein containing an amino acid sequence, which is the same or substantially the same as the amino acid sequence represented by SEQ ID NO:1 (preferably, a protein having a GABA transporter activity) or its partial peptide, or its amide or ester, or a salt thereof;
(vii) a method of screening a compound that alters a GABA transporter activity of the protein containing an amino acid sequence, which is the same or substantially the same as the amino acid sequence represented by SEQ ID NO:1 (preferably, a protein having a GABA transporter activity), or its salt;
(viii) a compound or its salt obtainable by the screening method; and,
(ix) a pharmaceutical comprising the compound or its salt.